Mounting evidence suggests that disturbances in phosphorus metabolism contribute to excess cardiovascular disease events and death independently of established risk factors. Excess dietary phosphorus intake plays a central role in the pathogenesis of these disorders. In the US, dietary phosphorus consumption far exceeds current recommendations for daily intake, in large part due to the nearly ubiquitous distribution of phosphorus-based food additives in the US food supply. These additives are heavily utilized by the food manufacturing industry to enhance the taste, appearance, and shelf-life of processed foods and thus, can substantially augment daily phosphorus intake in persons consuming convenience and fast foods typical of the American diet. While currently considered safe for public consumption by the US Food and Drug administration, recent data suggest that high intake of these additives may have important health consequences. High intake of phosphorus additives impaired cardiovascular health in animal and human studies. In addition, higher phosphorus intake stimulates the secretion of phosphorus-regulatory hormones such as fibroblast growth factor 23 (FGF23), elevated levels of which were associated with inflammation, cardiovascular disease events and death. These data suggest that excess intake of phosphorus-based food additives is an important and potentially modifiable risk factor for disturbed phosphorus metabolism, inflammation, and cardiovascular disease among millions of individuals consuming typical American diets. However, few physiological studies specifically examined the effect of excess commercial phosphorus additive intake on phosphate metabolism and cardiovascular function in healthy volunteers. This is the central focus of this application. Specifically, we will (1) determine the effect of additive-enhanced foods on blood phosphate and FGF23 levels, and biomarkers of inflammation, and (2) determine the effect of additive-enhanced foods on vascular reactivity in healthy volunteers. Participants will consume standardized diets prepared by the metabolic kitchen of the University of Alabama Clinical Research Unit over a 4-week period of time. Blood and urine parameters will be collected throughout the dietary intervention periods to assess study outcome variables. In addition, brachial artery flow mediated dilatation will be assessed before and after the dietary interventions to determine the effects of phosphorus additives on vascular function. These results will provide critical pilot data for the design and implementation of futur interventional studies aimed at examining the impact of modulating phosphorus-based food additives on mineral metabolism and cardiovascular health across the spectrum of kidney disease. PUBLIC HEALTH RELEVANCE: Cardiovascular diseases (CVD) remain the major cause of death in the US. Disturbances in phosphorus metabolism are strongly linked to CVD, and thus, may be modifiable targets of therapy. The proposed studies will examine the role of excess phosphorus-based food additive intake in the pathogenesis of disordered phosphorus metabolism in healthy volunteers, which will help clarify the potential public health implications of the nearly ubiquitous distribution of phosphorus-based food additives in the US food supply